Findings
Early and iterative engagement with EMA helps developers refine data generation plans, identify multidisciplinary expertise, and ensure the adequacy of early-stage data.
Clearly defining the concept of interest, context of use, and clinically meaningful change is essential for qualifying digital measures.
Comprehensive documentation should cover benefit-risk impacts, reliability, and validity of digital health technologies, avoiding overly detailed technical specifications that could invalidate qualification during updates.
Risk assessments of technology changes and updates, akin to approaches used for manufacturing changes, are crucial during regulatory reviews.
Support for collaborative groups, such as consortia and trade associations, helps aggregate and harmonize data to progress regulatory applications.

Recommendations
Establish early contact with EMA to align on regulatory requirements, optimize data generation, and ensure continuity in assessment teams.
Identify the digital technology’s impact on benefit-risk assessment, specifying its purpose as a novel measure or alternative to traditional methods.
Provide evidence of reliability, accuracy, repeatability, and clinical validity, ensuring sufficient detail for regulatory assessment without risking qualification during updates.
Conduct comprehensive risk assessments for changes to technology or software, following principles of ICH guidelines (Q8, Q9, Q10, Q12).
Develop user manuals and training materials to optimize implementation in clinical trials and ensure patient compliance.

Regulatory Considerations
EMA’s Remit: Focus on aspects affecting the benefit-risk assessment of medicinal products, while providing high-level information on unrelated technical parameters.
Alignment with MDR and GDPR: Ensure digital tools comply with applicable legal frameworks, including medical device regulations and data protection requirements.
Treat software and technology updates with a risk-based framework, evaluating their impact on clinical data validity and performance.
Collaborate with consortia to aggregate diverse data sources for confidential regulatory discussions, maximizing evidentiary value.
For medical devices, ensure CE marking or equivalent regulatory compliance before marketing, though it is not required during development.